Primary Osteoarthritis of Knee Nos
Conditions
Brief summary
The purpose of this study is to determine 1) the effective dosage of intra-articular tranexamic acid injection for controlling blood loss and blood transfusion requirement in conventional total knee replacement, and 2) whether the blood loss reduction effect depended on the dose of tranexamic acid used.
Interventions
DRUGTranexamic Acid
Inject tranexamic acid solution intra-articularly after fascia closure
Use physiologic saline for mixing with tranexamic acid or use alone in placebo group
Sponsors
Mahidol University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* patients diagnosed as primary knee osteoarthritis and underwent unilateral primary cemented conventional total knee replacement * no risk of abnormal bleeding tendency or bleeding disorder (normal coagulogram, serum creatinine \< 2.0 mg/dL, stop nonsteroidal anti-inflammatory drugs and antiplatelet drugs more than 7 days * no contra-indication for tranexamic acid use (no active intravascular clotting process, no acquired defective colour vision, no subarachnoid hemorrhage, no hypersensitivity to TXA, and no any of history of serious adverse effects, thrombotic disorder and hematuria)
Exclusion criteria
* incomplete data collection, for example, malfunctioned drain or accidental drain removal.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Perioperative Blood Loss | 5 days after surgery | * Drainage blood loss measured by accumulating total drainage volume postoperatively * Calculated total blood loss measured by using specific formula and difference between hematocrit preoperatively and the fourth postoperative day |
| Total Hemoglobin Loss | 5 days after surgery | Total hemoglobin loos measured by difference between hemoglobin preoperatively and the fourth postoperative day |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Knee Function Scores | 1 year after surgery | Knee function score was measured with 2 methods, and were evaluated preoperatively and then postoperatively at 3-month, 6-month, and 1-year period. 1. Knee Society Knee Score using for rating knee function measurement and subdivided into two parts; knee score and function score 1.1. Knee score : calculated from pain, presence of deformity, total range of flexion, alignment, and stability. Total score is 100 (0-100), more score means better. 1.2. Function score : calculated from patient's ability to walk and climb stairs. The score ranges from 0-100, more score means better. 2. Western Ontario and McMaster Universities Arthritis Index or WOMAC score : a widely used, standardized questionnaires for evaluating the condition of patients with knee osteoarthritis, including pain (score = 0-20), stiffness (0-8), and functional limitation (0-68). Total score ranges from 0-68, lower score means better. |
| Number of Patients Required Blood Transfusion | postoperative period (5 days after surgery) | — |
| Number of Patients Having Postoperative Complications | postoperative 1-year period | Postoperative complications were measured as an incidence of the following complications; * wound hematoma * surgical site infection * systemic infection * deep vein thrombosis * pulmonary embolism * knee stiffness requiring manipulation * medical complication such as myocardial infarction, congestive hear failure |
Countries
Thailand
Participant flow
Recruitment details
The patients, who planned to undergo primary total knee replacement, were recruited from medical clinics before setting the operative schedule between 2009 and 2010.
Pre-assignment details
Seventeen patients were excluded that including refusal to participate (4 patients), serum creatinine more than 2.0 mg% (4 patients), rheumatoid arthritis (4 patients), abnormal coagulogram (3 patients), and history of stroke (2 patients)
Participants by arm
| Arm | Count |
|---|---|
| Control Group physiologic saline 25 ml
Physiologic saline : Use physiologic saline for mixing with tranexamic acid or use alone in placebo group | 45 |
| TXA-250 Group A total of 25-ml solution with 250-mg tranexamic acid
Physiologic saline : Use physiologic saline for mixing with tranexamic acid or use alone in placebo group
Tranexamic Acid : Inject tranexamic acid solution intra-articularly after fascia closure | 45 |
| TXA-500 Group A total of 25-ml solution with 500-mg tranexamic acid
Physiologic saline : Use physiologic saline for mixing with tranexamic acid or use alone in placebo group
Tranexamic Acid : Inject tranexamic acid solution intra-articularly after fascia closure | 45 |
| Total | 135 |
Baseline characteristics
| Characteristic | TXA-250 Group | TXA-500 Group | Control Group | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 25 Participants | 32 Participants | 25 Participants | 82 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 13 Participants | 20 Participants | 53 Participants |
| Age Continuous | 67.6 years STANDARD_DEVIATION 8.7 | 68.1 years STANDARD_DEVIATION 6.2 | 66.2 years STANDARD_DEVIATION 7.3 | 67.3 years STANDARD_DEVIATION 7.5 |
| Region of Enrollment Thailand | 45 participants | 45 participants | 45 participants | 135 participants |
| Sex: Female, Male Female | 42 Participants | 40 Participants | 43 Participants | 125 Participants |
| Sex: Female, Male Male | 3 Participants | 5 Participants | 2 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 45 | 0 / 45 | 0 / 45 |
| serious Total, serious adverse events | 4 / 45 | 1 / 45 | 2 / 45 |
Outcome results
Primary
Perioperative Blood Loss
* Drainage blood loss measured by accumulating total drainage volume postoperatively * Calculated total blood loss measured by using specific formula and difference between hematocrit preoperatively and the fourth postoperative day
Time frame: 5 days after surgery
Population: Using intention-to-treat analysis
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Control Group | Perioperative Blood Loss | Drainage blood loss | 546.9 ml | Standard Deviation 273 |
| Control Group | Perioperative Blood Loss | Calculated total blood loss | 329.2 ml | Standard Deviation 119.4 |
| TXA-250 Group | Perioperative Blood Loss | Drainage blood loss | 475.0 ml | Standard Deviation 254.4 |
| TXA-250 Group | Perioperative Blood Loss | Calculated total blood loss | 239.7 ml | Standard Deviation 83.7 |
| TXA-500 Group | Perioperative Blood Loss | Drainage blood loss | 430.2 ml | Standard Deviation 224 |
| TXA-500 Group | Perioperative Blood Loss | Calculated total blood loss | 217.2 ml | Standard Deviation 86.1 |
p-value: <0.05ANOVA
p-value: <0.05ANOVA
Primary
Total Hemoglobin Loss
Total hemoglobin loos measured by difference between hemoglobin preoperatively and the fourth postoperative day
Time frame: 5 days after surgery
Population: Use intention-to-treat analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Group | Total Hemoglobin Loss | 2.9 g/dL | Standard Deviation 1.2 |
| TXA-250 Group | Total Hemoglobin Loss | 2.2 g/dL | Standard Deviation 0.7 |
| TXA-500 Group | Total Hemoglobin Loss | 2.2 g/dL | Standard Deviation 0.7 |
p-value: 0.05ANOVA
Secondary
Knee Function Scores
Knee function score was measured with 2 methods, and were evaluated preoperatively and then postoperatively at 3-month, 6-month, and 1-year period. 1. Knee Society Knee Score using for rating knee function measurement and subdivided into two parts; knee score and function score 1.1. Knee score : calculated from pain, presence of deformity, total range of flexion, alignment, and stability. Total score is 100 (0-100), more score means better. 1.2. Function score : calculated from patient's ability to walk and climb stairs. The score ranges from 0-100, more score means better. 2. Western Ontario and McMaster Universities Arthritis Index or WOMAC score : a widely used, standardized questionnaires for evaluating the condition of patients with knee osteoarthritis, including pain (score = 0-20), stiffness (0-8), and functional limitation (0-68). Total score ranges from 0-68, lower score means better.
Time frame: 1 year after surgery
Population: Using intention-to-treat analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | Knee Function Scores | Knee Society Knee score at 1 year | 148.9 units on a scale | Standard Deviation 10.1 |
| Control Group | Knee Function Scores | WOMAC score at 1 year | 15.5 units on a scale | Standard Deviation 6.6 |
| TXA-250 Group | Knee Function Scores | Knee Society Knee score at 1 year | 151.2 units on a scale | Standard Deviation 9.1 |
| TXA-250 Group | Knee Function Scores | WOMAC score at 1 year | 15.1 units on a scale | Standard Deviation 6.2 |
| TXA-500 Group | Knee Function Scores | Knee Society Knee score at 1 year | 150.9 units on a scale | Standard Deviation 9.3 |
| TXA-500 Group | Knee Function Scores | WOMAC score at 1 year | 14.5 units on a scale | Standard Deviation 7.1 |
p-value: <0.05ANOVA
p-value: <0.05ANOVA
Secondary
Number of Patients Having Postoperative Complications
Postoperative complications were measured as an incidence of the following complications; * wound hematoma * surgical site infection * systemic infection * deep vein thrombosis * pulmonary embolism * knee stiffness requiring manipulation * medical complication such as myocardial infarction, congestive hear failure
Time frame: postoperative 1-year period
Population: Using Intention-to-treat analysis
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control Group | Number of Patients Having Postoperative Complications | Venous thromboembolic complication | 4 participants |
| Control Group | Number of Patients Having Postoperative Complications | Re-dressing incidence | 3 participants |
| Control Group | Number of Patients Having Postoperative Complications | Re-clamp incidence | 6 participants |
| Control Group | Number of Patients Having Postoperative Complications | Congestive heart failure | 0 participants |
| TXA-250 Group | Number of Patients Having Postoperative Complications | Congestive heart failure | 1 participants |
| TXA-250 Group | Number of Patients Having Postoperative Complications | Re-clamp incidence | 1 participants |
| TXA-250 Group | Number of Patients Having Postoperative Complications | Re-dressing incidence | 0 participants |
| TXA-250 Group | Number of Patients Having Postoperative Complications | Venous thromboembolic complication | 1 participants |
| TXA-500 Group | Number of Patients Having Postoperative Complications | Re-clamp incidence | 0 participants |
| TXA-500 Group | Number of Patients Having Postoperative Complications | Congestive heart failure | 0 participants |
| TXA-500 Group | Number of Patients Having Postoperative Complications | Venous thromboembolic complication | 2 participants |
| TXA-500 Group | Number of Patients Having Postoperative Complications | Re-dressing incidence | 0 participants |
p-value: <0.05Fisher Exact
Secondary
Number of Patients Required Blood Transfusion
Time frame: postoperative period (5 days after surgery)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control Group | Number of Patients Required Blood Transfusion | 10 participants |
| TXA-250 Group | Number of Patients Required Blood Transfusion | 6 participants |
| TXA-500 Group | Number of Patients Required Blood Transfusion | 0 participants |
p-value: <0.05Fisher Exact